rs3088190

Variant names:

• chr12-14829418-G-C
• rs3088190
• NM_021071.4:c.898C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_021071.4(ART4):​c.898C>G​(p.Leu300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,606,268 control chromosomes in the GnomAD database, including 11,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1312 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9864 hom.)
• Consequence: ART4 NM_021071.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.332
• Publications: 16 publications found

Genes affected

ART4 (HGNC:726): (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)) This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

ENSG00000256339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039037168).
• BP6: Variant 12-14829418-G-C is Benign according to our data. Variant chr12-14829418-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060827.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	NM_021071.4	MANE Select	c.898C>G	p.Leu300Val	missense	Exon 3 of 3	NP_066549.2	Q93070

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.898C>G	p.Leu300Val	missense	Exon 3 of 3	ENSP00000228936.4	Q93070
	ART4	ENST00000430129.6	TSL:1	c.*12C>G		3_prime_UTR	Exon 3 of 3	ENSP00000412735.2	Q3KZ30
	ART4	ENST00000544616.5	TSL:1	c.*12C>G		3_prime_UTR	Exon 2 of 2	ENSP00000442877.1	Q3KZ29

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18240 AN: 152010 Hom.: 1304 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.129 AC: 32062 AN: 247736 AF XY: 0.119

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.0747

Gnomad EAS exome AF: 0.0844

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.0939

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.106 AC: 154611 AN: 1454140 Hom.: 9864 Cov.: 30 AF XY: 0.104 AC XY: 74862 AN XY: 723294

African (AFR) AF: 0.117 AC: 3899 AN: 33216

American (AMR) AF: 0.326 AC: 14161 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.0748 AC: 1947 AN: 26018

East Asian (EAS) AF: 0.0841 AC: 3308 AN: 39352

South Asian (SAS) AF: 0.0772 AC: 6538 AN: 84716

European-Finnish (FIN) AF: 0.152 AC: 8059 AN: 53188

Middle Eastern (MID) AF: 0.0357 AC: 205 AN: 5750

European-Non Finnish (NFE) AF: 0.0995 AC: 110276 AN: 1108384

Other (OTH) AF: 0.104 AC: 6218 AN: 60070

GnomAD4 genome AF: 0.120 AC: 18278 AN: 152128 Hom.: 1312 Cov.: 32 AF XY: 0.125 AC XY: 9295 AN XY: 74372

African (AFR) AF: 0.120 AC: 4989 AN: 41504

American (AMR) AF: 0.227 AC: 3462 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3470

East Asian (EAS) AF: 0.0897 AC: 464 AN: 5174

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4824

European-Finnish (FIN) AF: 0.158 AC: 1667 AN: 10554

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6708 AN: 68012

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.0991 Hom.: 579

Bravo AF: 0.129

TwinsUK AF: 0.104 AC: 386

ALSPAC AF: 0.102 AC: 392

ESP6500AA AF: 0.115 AC: 508

ESP6500EA AF: 0.0978 AC: 841

ExAC AF: 0.123 AC: 14905

Asia WGS AF: 0.115 AC: 399 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ART4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.76
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.022	N
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.33
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.0030
Sift	Benign	0.12	T
Sift4G	Uncertain	0.027	D
Vest4		0.035
MPC		0.0097
ClinPred		0.0049	T
GERP RS		-5.7
gMVP		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3088190; hg19: chr12-14982352; COSMIC: COSV57451649;